Apart from the trailblazing hybrid of the Mercedes-Benz S400 Hybrid, the range of engines for the 2010 Mercedes-Benz S-Class comprises eight other powerful units: two diesel variants and six petrol engines with six, eight and twelve cylinders. Detailed fine-tuning of these engines has been supplemented with addition fuel economy measures as part of the BlueEFFICIENCY package. These include aerodynamic optimisation, demand-controlled fuel pumps and the fuel-efficient gearshift programme for the standard 7G-TRONIC automatic transmission. These measures have enabled Mercedes-Benz developers to reduce fuel consumption and CO2 emissions by up to seven percent compared to the preceding models. By means of additional well-aimed aerodynamic measures, the Mercedes-Benz engineers have also managed to reduce wind noise, thus further enhancing the standard of ride comfort.

With diesel fuel consumption of 7.6 litres per 100 kilometres and CO2 emissions of 199-201 grams per kilometre, the S350 CDI BlueEFFICIENCY (173 kW/ 235 hp) likewise boasts outstanding figures for the luxury class. Mercedes-Benz achieves this exemplary efficiency with a tailor-made BlueEFFICIENCY package, which also includes closed underbody panelling and decoupling of the 7G‑TRONIC automatic transmission at standstill.

The 3.0 litre diesel engine is also used in the S350 CDI 4MATIC. The second diesel variant is the eight-cylinder S 450 CDI(235 kW/320 hp) with a displacement of 4.0 litres. The range of petrol engines comprises the six-cylinder S350/ S350 4MATIC (200 kW/272 hp) with a displacement of 3.5 litres and the two eight-cylinder units in the S 450/S 450 4MATIC (250 kW/340 hp; displacement 4.7 litres) and S 500/S 500 4MATIC (285 kW/388 hp; displacement 5.5 litres). The flagship model is still the S600 with the 380 kW/517 hp twelve-cylinder biturbo unit (displacement 5.5 litres), which accelerates the luxury saloon to 100 km/h in 4.6 seconds. The Mercedes-AMG high-performance contributions to the range are the S 63 AMG with its 386 kW/525 hp V8 engine (displacement 6.2 litres) and the S 65 AMGwith a 450 kW/612 hp twelve-cylinder engine (displacement 6.0 litres).